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A novel role for Gab2 in bFGF-mediated cell survival during retinoic acid–induced neuronal differentiation

Gab proteins amplify and integrate signals stimulated by many growth factors. In culture and animals, retinoic acid (RA) induces neuronal differentiation. We show that Gab2 expression is detected in neurons in three models of neuronal differentiation: embryonic carcinoma (EC) stem cells, embryonic s...

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Detalles Bibliográficos
Autores principales: Mao, Yingwei, Lee, Angel W.-M.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171408/
https://www.ncbi.nlm.nih.gov/pubmed/16009726
http://dx.doi.org/10.1083/jcb.200505061
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author Mao, Yingwei
Lee, Angel W.-M.
author_facet Mao, Yingwei
Lee, Angel W.-M.
author_sort Mao, Yingwei
collection PubMed
description Gab proteins amplify and integrate signals stimulated by many growth factors. In culture and animals, retinoic acid (RA) induces neuronal differentiation. We show that Gab2 expression is detected in neurons in three models of neuronal differentiation: embryonic carcinoma (EC) stem cells, embryonic stem cells, and primary neural stem cells (NSCs). RA treatment induces apoptosis, countered by basic FGF (bFGF). In EC cells, Gab2 silencing results in hypersensitivity to RA-induced apoptosis and abrogates the protection by bFGF. Gab2 suppression reduces bFGF-dependent activation of AKT but not ERK, and constitutively active AKT, but not constitutively active MEK1, reverses the hypersensitization. Thus, Gab2-mediated AKT activation is required for bFGF's protection. Moreover, Gab2 silencing impairs the differentiation of EC cells to neurons. Similarly, in NSCs, Gab2 suppression reduces bFGF-dependent proliferation as well as neuronal survival and production upon differentiation. Our findings provide the first evidence that Gab2 is an important player in neural differentiation, partly by acting downstream of bFGF to mediate survival through phosphoinositide 3 kinase–AKT.
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spelling pubmed-21714082008-03-05 A novel role for Gab2 in bFGF-mediated cell survival during retinoic acid–induced neuronal differentiation Mao, Yingwei Lee, Angel W.-M. J Cell Biol Research Articles Gab proteins amplify and integrate signals stimulated by many growth factors. In culture and animals, retinoic acid (RA) induces neuronal differentiation. We show that Gab2 expression is detected in neurons in three models of neuronal differentiation: embryonic carcinoma (EC) stem cells, embryonic stem cells, and primary neural stem cells (NSCs). RA treatment induces apoptosis, countered by basic FGF (bFGF). In EC cells, Gab2 silencing results in hypersensitivity to RA-induced apoptosis and abrogates the protection by bFGF. Gab2 suppression reduces bFGF-dependent activation of AKT but not ERK, and constitutively active AKT, but not constitutively active MEK1, reverses the hypersensitization. Thus, Gab2-mediated AKT activation is required for bFGF's protection. Moreover, Gab2 silencing impairs the differentiation of EC cells to neurons. Similarly, in NSCs, Gab2 suppression reduces bFGF-dependent proliferation as well as neuronal survival and production upon differentiation. Our findings provide the first evidence that Gab2 is an important player in neural differentiation, partly by acting downstream of bFGF to mediate survival through phosphoinositide 3 kinase–AKT. The Rockefeller University Press 2005-07-18 /pmc/articles/PMC2171408/ /pubmed/16009726 http://dx.doi.org/10.1083/jcb.200505061 Text en Copyright © 2005, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Mao, Yingwei
Lee, Angel W.-M.
A novel role for Gab2 in bFGF-mediated cell survival during retinoic acid–induced neuronal differentiation
title A novel role for Gab2 in bFGF-mediated cell survival during retinoic acid–induced neuronal differentiation
title_full A novel role for Gab2 in bFGF-mediated cell survival during retinoic acid–induced neuronal differentiation
title_fullStr A novel role for Gab2 in bFGF-mediated cell survival during retinoic acid–induced neuronal differentiation
title_full_unstemmed A novel role for Gab2 in bFGF-mediated cell survival during retinoic acid–induced neuronal differentiation
title_short A novel role for Gab2 in bFGF-mediated cell survival during retinoic acid–induced neuronal differentiation
title_sort novel role for gab2 in bfgf-mediated cell survival during retinoic acid–induced neuronal differentiation
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171408/
https://www.ncbi.nlm.nih.gov/pubmed/16009726
http://dx.doi.org/10.1083/jcb.200505061
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